The objective of this study is to delineate biochemical defects and to correlate the clinical characteristics with the biochemical defects in heritable disorders of collagen metabolism, and to elucidate the principle of collagen and protein biosynthesis from such experiments of nature. The present study of abnormalities of collagen metabolism is made feasible by advances in the understanding of collagen biosynthesis and the genetic types of collagen, as well as the development of methodology for the study of collagen metabolism in cell culture and from small tissue specimens. The specific areas of abnormal collagen metabolism proposed for study are: 1) The study of procollagen peptidase deficiency in humans through a) The development of a specific rapid assay for the enzymes converting the collagen precursors to collagen. b) Analysis of the collagenous proteins synthesized by cultured skin fibroblasts derived from patients with procollagen peptidase deficiency. c) Delineation of the mechanism for increased collagenous protein synthesis in these cultured fibroblasts. 2) The elucidation of defects in collagen metabolism in two forms of osteogenesis imperfecta in which there are a) An altered ratio of type I to type III collagen biosynthesis in cell culture. b) An abnormal pepsin sensitive type I collagen synthesized in cell culture. 3) The elucidation of the mechanism for decreased type III collagen synthesis in tissues and cultured cells from patients with Ehlers-Danlos type IV.